This is a competing continuation of R37-MH-43454 which received a MERIT award at the time of its last competitive renewal. This application seeks five additional years of support to continue the PI's research program on the neural substrates of affective style and emotion regulation. Individual differences in affective style and emotion regulation determine variation in stress responsivity and vulnerability to mood and anxiety disorders. The broad goal of this application is to further understand the neural circuitry that underlies individual differences in emotion regulation and to determine the nomological network of associations with these individual differences. Work is proposed that also extends this work to patients with major depression to further our understanding of the nature of emotion regulation abnormalities in this disorder. In the first study, a large sample of community volunteers will be tested using peripheral psychophysiological measures (startle and corrugator EMG) to characterize relations between individual differences in emotional reactivity and emotion regulation and to select individuals showing stable and extreme profiles on these measures for subsequent intensive study. In follow-up studies with these selected extreme groups, fMRI studies of neural circuitry underlying voluntary regulation of emotion in response to both negative and positive emotional pictures and to thermal pain will be evaluated. In addition, these individuals will undergo two Trier Social Stress Tests (TSST) to examine cortisol response and habituation to psychosocial stress. In addition, behavioral measures of cognitive and affective conflict processing will be obtained. Structured clinical interviews will be conducted on parents of probands to examine family history of psychopathology in the extreme groups. Finally, an independent sample of patients with major depression and matched controls will be scanned using the identical paradigms for the assessment of the voluntary regulation of affect to examine how abnormalities in the circuitry of emotion regulation are related to heterogeneity of symptoms in depression. This work will provide critical new information on the neurobiology of affective style. These new data will further our understanding of endophenotypes of affective processing that are associated with vulnerability to psychopathology. [unreadable] [unreadable] [unreadable]